Eliminating leprosy as a public health problem--is the optimism justified?

Systematic use of multidrug therapy has proved to be so effective that leprosy can be eliminated as a public health problem by the end of the century. However, because of the long incubation period of this disease, together with the time-lag in case detection, the factors involved in achieving and sustaining its elimination have to be very carefully defined.

A case of relapse with drug-susceptible M. leprae after multidrug therapy.

A male born in 1930 was diagnosed as smear-positive borderline leprosy in 1971, and was treated with dapsone and/or sulfamethoxypyridazine from 1972 to 1980 with clinical improvement. However, new skin lesions with smears strongly positive appeared in August 1980, and he was diagnosed as having downgraded to lepromatous (LL) leprosy, but the bacilli recovered from the skin biopsy were fully susceptible to both dapsone and rifampin by mouse foot pad technique. Between 1981 and 1983, the patient was treated with 24 months of rifampin 600 mg and dapsone 100 mg daily, supplemented with prothionamide 500 mg daily during the initial 3 months, and his skin lesions gradually improved during treatment with the combined regimen. Afterward, the patient was kept under surveillance without treatment. From 1984 to 1986, his skin smears were negative, and no bacilli could be found from a skin biopsy taken in 1985. Then in 1987, 52 months after stopping treatment, new skin lesions appeared with a high concentration of Mycobacterium leprae (2 x 10(6)/mg tissue). The drug-susceptibility test again demonstrated that the organisms were fully susceptible to both dapsone and rifampin. Apparently the relapse was due to remultiplication of drug-susceptible persisters.

Technical problems related to multidrug therapy in leprosy control.

About 40% of registered leprosy patients worldwide have been, or are being, treated with multidrug therapy (MDT) in accordance with the standard regimens recommended by WHO in 1981. The conclusions that can be drawn from such an extensive experience are discussed. The most significant of these are: (i) the MDT regimens recommended by WHO are non-toxic and well-accepted by patients; (ii) as regards the efficacy of these regimens, post-therapeutic relapses, in both multibacillary and paucibacillary patients, have been negligible when observed over periods of one to three years. The overall conclusion that at present emerges is that the MDT regimens for leprosy control, as recommended by WHO in 1981, should continue to be applied without any modification.

BCG vaccination of children against leprosy: fourteen-year findings of the trial in Burma.

The value of BCG vaccination in preventing leprosy among children was studied in an area of high leprosy endemicity in Burma through a controlled trial; one group of 13 066 children received BCG and another group of 13 176 served as controls. The overall protective effect of BCG, which was only about 20% over the 14-year period, was found to vary with the batch of vaccine, as well as age, sex, and contact status of the children. BCG protection was found to be independent of the initial tuberculin status of the children. The protective effect of BCG against the lepromatous type of leprosy could not be measured because of the low incidence. Protection was observed throughout the fourteen years of the study except for the first year. The results are compared with those of three other major BCG trials in leprosy. The trial has shown that BCG provides only a very modest level of protection and that BCG vaccination is not likely to be an important solution for leprosy control.

BCG vaccination of children against leprosy: fourteen-year findings of the trial in Burma

The value of BCG vaccination in preventing leprosy among children was studied in an area of high leprosy endemicity in Burma through a controlled trial; one group of 13066 children received BCG and another group of 13176 served as controls. The overall protective effect of BCG, which was only about 20% over the 14-year period, was found to vary with the batch of vaccine, as well as age, sex, and contacts status the children. The protective effect of BCG against the lepromatous type of leprosy could not be measured because of the low incidence. Protection was observed throught the fourteen years of the study except for the firts year. The results are compared with those of three other major BCG trials in leprosy. The trial has shown that BCG provides only a very modest level of protection and that BCG vaccination is not likely to be an important solution for leprosy control.

Immunization against leprosy: progress and prospects.

The limitations of the current approach to leprosy control through mass treatment of patients are well recognized. The long incubation period of the disease, the insidious onset, the chronic course, and the need for prolonged treatment have made control a formidable task. The recent years have seen tremendous progress in the field of immunology of leprosy, and the availability of large quantities of Mycobacterium leprae, grown in the nine-banded armadillo, has given impetus to the search for a vaccine specific for leprosy. Methods for production and purification of M. leprae have now been developed and the resulting preparation has been shown to produce good delayed-type hypersensitivity in mice and guinea pigs.Small-scale studies in human subjects have shown that preparations of M. leprae and BCG can induce cell-mediated immunity in Mitsuda-negative patients and contacts. It is now appropriate to consider field trials of vaccine preparations in selected groups before moving on to large-scale trials in different populations.

Immunization against leprosy: progress and prospects.

PIP: The complex biology of the leprosy organism, the course of the disease, and the atypical human immune response to both vaccination and infection by Mycobacterium leprae are reviewed. Since the 1960s several trials of vaccination with BCG, the tuberculosis-causing Mycobacterium related to the leprosy organism, have showed varied degrees of protection against leprosy. In the 1970s, M. leprae was grown for the first time, in captured wild armadillos, so material is now available for vaccine trials against leprosy itself. The material does indeed evoke delayed hypersensitivity and protective immunity in animal hosts. There are, however, several important difficulties in designing human trials with a M. leprae vaccine. The first is the paradox that lepromatous leprosy patients, who lack cell-mediated immunity to M. leprae, respond negatively to the lepromin skin test, while leprosy-free persons respond positively, since in them the skin test acts as a micro-vaccine. There are many practical and ethical factors to consider in planning vaccine trials, such as the obligation to give patients effective chemotherapy, which may obscure trial results. Another is the finding that a significant proportion of recipients in small-scale trials to date develop neuritis from vaccine. Studies suggest that combined BCG and M. leprae vaccines, and 2 other modified M. leprae strains developed in India, can induce cell-mediated immunity in leprosy patients. Some way must be found to monitor recipients in large-scale trials because of this, in other words, to distinguish bacteria-free leprosy patients who develop cellular mediated immunity from persons getting the disease. Development of an effective leprosy vaccine will be more economical than long-term drug treatment, but it will take at least 10 years before successful, large trials are completed.^ieng